This application addresses one of the five thematic areas in the RFA-OD-10-005: Focusing on Global Health. Electronic waste (e-waste) has become a global environmental health problem because of its huge amount of production worldwide--approximately 20-50 million tons per year. E-waste contains high levels of several metals (lead [Pb], mercury [Hg], cadmium [Cd], chromium [Cr], manganese [Mn], etc.), but inappropriate and unregulated recycling exposes the workers and residents in many towns and villages in developing countries. Public health investigations into the exposure levels and potential toxicity in vulnerable population are urgently needed to address this critical environmental health problem. This research is closely related to NIH mission on global health to reduce preventable morbidity and mortality in developing countries. Developing fetuses and young children are especially susceptible to environmental toxicants. The metal mixture in e-waste is unique in its composition and concentrations, but the toxicity of this complex exposure is virtually unknown in developing fetuses and young children. The long-term goal is to investigate developmental effects of e-waste toxicant mixtures and provide human study evidence to inform future regulatory actions and public health prevention. The application will address this global health problem by recruiting 600 pregnant women (300 from an e-waste recycling site and 300 from a control site in China) and following up to 9 months postpartum. The applicants will accomplish three Specific Aims: 1) Characterize the e-waste metal mixture exposure in pregnant women and their fetuses;2) Examine adverse pregnancy outcomes associated with e-waste metal mixture exposure;and 3) Investigate neurodevelopmental toxicity and thyroid hormone disruption of e-waste metal mixture exposure. The applicants will assess the environmental (air, dust, soil) and biological (maternal blood, urine, hair, cord blood) exposure markers of e-waste metal mixtures (Pb, Hg, Cd, Cr, Mn). Pregnancy outcomes (stillbirth, gestational length, preterm birth, birth weight, small for gestational age [SGA], birth length, head circumference, anogenital distance [AGD]), thyroid hormones (TSH, T4, T3), and infant neurodevelopment (Bayley Scales of Infant Development-2 [BSID-2]) will be examined. This study will provide novel data about metal toxicants in e-waste and developmental outcomes in humans, increase scientific knowledge about rarely studied mixture exposure, and inform environmental health policy making to reduce e- waste toxicant exposure in developing countries. PUBLIC HEALTH RELEVANCE: The proposed study will address a critical issue of global environmental health--enormous e-waste production but with prevailing primitive recycling in developing countries. This study will address the developmental effects of metal mixtures from primitive e-waste recycling activities. It will inform environmental health policy making to manage the e-waste and protect human health.